Glucose‐lowering activity of the dipeptidyl peptidase‐4 inhibitor saxagliptin in drug‐naive patients with type 2 diabetes*

Rosenstock, Julio; Sankoh, Serap; List, James F.

doi:10.1111/j.1463-1326.2008.00876.x

Cited by 218 publications

(196 citation statements)

References 15 publications

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“…74 When added to metformin the most frequently reported side-effects with incidence rates above 5% (all comparisons are saxagliptin 2.5 to 10 mg + metformin vs. placebo + metformin) were nasopharingytis (8.7% vs. 7.8%), headache (8% vs. 7.3%), diarrhoea (7.1% vs. 11.2%), upper respiratory tract infection (6.6% vs. 5%), influenza (6% vs. 7.3%), urinary tract infection (5.1% vs. 4.5%), back pain (4.3% vs. 6.7%), and pain in the extremities (3% vs. 5.6%). The addition of saxagliptin to metformin did not augment the gastrointestinal intolerability of metformin.…”

Section: Saxagliptinmentioning

confidence: 99%

“…81 Saxagliptin is weight neutral in monotherapy or in combination with metformin. [72][73][74] In combination with glyburide a small (1 kg) but significant weight gain compared with glyburide alone was observed in parallel with improved glycemic control. 71 Small, reversible dose-dependent reductions in absolute lymphocyte count (up to -0.38 × 10 3 cells/µl) which remained within the normal range have been observed, particularly in patients receiving doses above 20 mg daily, but no associated impaired immune function has been demonstrated.…”

Section: Saxagliptinmentioning

confidence: 99%

“…70 In drugnaïve patients with T2DM, saxagliptin 2.5-100 mg monotherapy once daily showed a similar tolerability profile to placebo, with a very low incidence of confirmed hypoglycemia (50 mg/dL) in the saxagliptin treatment arms. 74,80 When given as add-on treatment in patients with inadequate glycemic control, despite monotherapy with metformin, a TZD, or a sulphonylurea, saxagliptin 2.5-10 mg did not increase the risk of hypoglycaemia. 72,76,81 The frequency of confirmed hypoglycemia is reported in Table 1.…”

Section: Saxagliptinmentioning

confidence: 99%

“…71 Small, reversible dose-dependent reductions in absolute lymphocyte count (up to -0.38 × 10 3 cells/µl) which remained within the normal range have been observed, particularly in patients receiving doses above 20 mg daily, but no associated impaired immune function has been demonstrated. 73,74 In an open label study of a single dose of saxagliptin 10 mg the systemic exposure of saxagliptin correlated with the degree of renal impairment (1.2-4.5 fold higher than that in normal renal function). 84 In patients with end-stage renal disease, a 4-hour haemodialysis session removed 23% of saxagliptin.…”

Section: Saxagliptinmentioning

confidence: 99%

“…67 The efficacy of saxagliptin in patients with T2DM from published RCTs (randomised controlled trials), including saxagliptin monotherapy and combination therapy with sulphonylureas or metformin is summarized in Table 1. [71][72][73][74][75] Saxagliptin has also been examined in combination with TZD in a study of 565 patients with inadequate glycemic control (HbA 1c 7.0%-10.5%). Patients were randomized to receive add-on therapy with saxagliptin (2.5 mg or 5.0 mg) or placebo once daily, in addition to either pioglitazone (30 mg or 45 mg) or rosiglitazone (4 mg or 8 mg) for 24 weeks.…”

Section: Efficacymentioning

confidence: 99%

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Saxagliptin a New Second Line Therapy After Metformin for the Treatment of Type 2 Diabetes

Palalau¹,

Tahrani

Piya³

et al. 2010

Clinical Medicine Reviews in Vascular Health

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Type 2 diabetes mellitus (T2DM) is a major public health problem that affects an increasingly larger number of individuals worldwide. Metformin, unless contraindicated, is the recommended first line pharmacological treatment as it can achieve good glycemic control without weight gain or hypoglycemia and with evidence for cardioprotection. T2DM is a progressive disease, and consequently further therapeutic agents are needed in order to maintain good glycemic control and prevent long-term complications. These drugs are commonly associated with undesirable side effects such as weight gain and hypoglycaemia. Moreover, none have been proven to slow or prevent the progression of T2DM (which is mainly due to progressive β-cell failure). As a result, new agents based on newer therapeutic targets are needed. Incretin based therapy is the latest addition to the currently available anti diabetes treatment and includes two groups of agents: glucagon-like peptide-1 (GLP-1) analogues/mimetics and dipeptidyl peptidase-4 (DPP-4) inhibitors. These agents act either by supplying exogenous GLP-1 (GLP-1 analogues/mimetics) or by preventing the degradation of endogenous GLP-1 (DPP-4 inhibitors). GLP-1 is a gut hormone that is mainly secreted secondary to oral glucose ingestion and results in glucose-dependent insulin secretion and glucose-dependant glucagon suppression which in turn improve fasting and post-prandial glucose levels. GLP-1 is rapidly inactivated by the DPP-4 enzyme. There are several DPP-4 inhibitors currently available, including sitagliptin, vildagliptin and saxagliptin while others are in development. Due to their mechanism of action, DPP-4 inhibitors are associated with low risk of hypoglycemia and are weight neutral. As a result, they are attractive agents particularly in combination with metformin therapy. In this article we will examine the potential use of saxagliptin as an add-on therapy to metformin in patients with T2DM.

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Section: Saxagliptinmentioning

confidence: 99%

Section: Saxagliptinmentioning

confidence: 99%

Section: Saxagliptinmentioning

confidence: 99%

Section: Saxagliptinmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

See 3 more Smart Citations

Saxagliptin a New Second Line Therapy After Metformin for the Treatment of Type 2 Diabetes

Palalau¹,

Tahrani

Piya³

et al. 2010

Clinical Medicine Reviews in Vascular Health

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show abstract

Dipeptidyl Peptidase 4 Inhibitors

Weber

Thornberry

2010

Burger's Medicinal Chemistry and Drug Discovery

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Defective insulin secretion is a hallmark of type 2 diabetes (T2DM), and agents that increase the concentration of circulating insulin have proven beneficial in the treatment of diabetes. Dipeptidyl peptidase 4 (DPP‐4) inhibitors are a new oral approach to T2DM that lower glucose via stabilization of the incretin hormone glucagon‐like peptide 1 (GLP‐1), which has clearly established roles in insulin secretion and inhibition of glucagon production. These agents have been shown to produce clinically meaningful glucose control in a range of patients with type 2 diabetes without many of the liabilities that are associated with other oral therapies, including weight gain, edema, GI intolerability, and hypoglycemia. Accordingly, DPP‐4 inhibitors have excellent potential for use in both monotherapy and combination with established agents. Extensive structure–activity relationship (SAR) studies in many different laboratories have resulted in the identification of a number of clinical candidates. The most advanced of these have recently been approved for the treatment of T2DM, representing the first new oral therapy for treatment of this disease since the introduction of troglitazone in 1998.

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Dipeptidyl Peptidase 4 Inhibitors

Weber¹,

Thornberry²

2021

Burger's Medicinal Chemistry and Drug Discovery

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Type 2 diabetes (T2DM) is a growing worldwide epidemic. While a number of oral agents have been available to treat T2DM, they suffer from safety and tolerability issues and lack durability. In the 1990s, glucagon‐like peptide 1 (GLP‐1) emerged as a new approach to glucose lowering. Endogenous GLP‐1 is rapidly inactivated through the action of dipeptidyl peptidase 4 (DPP‐4), a serine dipeptidyl aminopeptidase that cleaves its N‐terminal two amino acids. Blocking DPP‐4 with a small molecule inhibitor was shown to increase circulating levels of GLP‐1 in rodent models and humans, leading to improved glucose control. Early DPP‐4 inhibitors were dipeptide mimetics, some of which bound to the DPP‐4 active site serine in a covalent manner. Screening and structure‐based drug design led to the identification of many other structural classes. In 2006, sitagliptin became the first DPP‐4 inhibitor approved by the FDA. Inhibitors now available include two for once‐weekly administration. Over 10 years of clinical experience has shown DPP‐4 inhibition to be safe and effective with a low risk of hypoglycemia, no weight gain, and no increased cardiovascular risk. Used as monotherapy or in combination with other glucose‐lowering medications, DPP‐4 inhibitors have become an important class of oral agents to treat T2DM.

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Glucose‐lowering activity of the dipeptidyl peptidase‐4 inhibitor saxagliptin in drug‐naive patients with type 2 diabetes*

Abstract: Saxagliptin effectively improved glycaemic control in drug-naive patients with T2DM and was generally safe, with a tolerability profile similar to placebo.

Cited by 218 publications

References 15 publications

Saxagliptin a New Second Line Therapy After Metformin for the Treatment of Type 2 Diabetes

Saxagliptin a New Second Line Therapy After Metformin for the Treatment of Type 2 Diabetes

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

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